The adenylate cyclase response to parathyroid hormone in fetal lung fibroblasts is enhanced by cortisol

1987 ◽  
Vol 7 (6) ◽  
pp. 503-508 ◽  
Author(s):  
Carolyn Lowe ◽  
Peter M. Barling ◽  
Stephen J. M. Skinner
Keyword(s):  
Parathyroid Hormone ◽  
Epithelial Cells ◽  
Adenylate Cyclase ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Osteosarcoma Cells ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Umr 106

Parathyroid hormone (PTH, <10−8 M) stimulated adenylate cyclase in fibroblasts, but not epithelial cells, isolated from fetal rat lung. In contrast to osteosarcoma cells (UMR 106), the response of fibroblasts to PTH was increased by pretreatment with cortisol (< 10−8-10−7 M).

Identification of Betamethasone-Regulated Target Genes and Cell Pathways in Fetal Rat Lung Mesenchymal Fibroblasts

Endocrinology ◽  
2019 ◽  
Vol 160 (8) ◽  
pp. 1868-1884 ◽  
Author(s):  
Bennet K L Seow ◽  
Annie R A McDougall ◽  
Kelly L Short ◽  
Megan J Wallace ◽  
Stuart B Hooper ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Preterm Birth ◽  
Transcriptome Sequencing ◽  
Target Genes ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Matrix Remodeling ◽  
Rat Lung ◽  
Fetal Rat ◽  
Fetal Rat Lung

Abstract Preterm birth is characterized by severe lung immaturity that is frequently treated antenatally or postnatally with the synthetic steroid betamethasone. The underlying cellular targets and pathways stimulated by betamethasone in the fetal lung are poorly defined. In this study, betamethasone was compared with corticosterone in steroid-treated primary cultures of fetal rat lung fibroblasts stimulated for 6 hours and analyzed by whole-cell transcriptome sequencing and glucocorticoid (GC) receptor (GR) chromatin immunoprecipitation sequencing (ChIP-Seq) analysis. Strikingly, betamethasone stimulated a much stronger transcriptional response compared with corticosterone for both induced and repressed genes. A total of 483 genes were significantly stimulated by betamethasone or corticosterone, with 476 stimulated by both steroids, indicating a strong overlap in regulation. Changes in mRNA levels were confirmed by quantitative PCR for eight induced and repressed target genes. Pathway analysis identified cell proliferation and cytoskeletal/cell matrix remodeling pathways as key processes regulated by both steroids. One target, transglutaminase 2 (Tgm2), was localized to fetal lung mesenchymal cells. Tgm2 mRNA and protein levels were strongly increased in fibroblasts by both steroids. Whole-genome GR ChIP-Seq analysis with betamethasone identified GC response element–binding sites close to the previously characterized GR target genes Per1, Dusp1, Fkbp5, and Sgk1 and near the genes identified by transcriptome sequencing encoding Crispld2, Tgm2, Hif3α, and Kdr, defining direct genomic induction of expression in fetal lung fibroblasts via the GR. These results demonstrate that betamethasone stimulates specific genes and cellular pathways controlling cell proliferation and extracellular matrix remodeling in lung mesenchymal fibroblasts, providing a basis for betamethasone’s treatment efficacy in preterm birth.

Hyperoxia inhibits fetal rat lung fibroblast proliferation and expression of procollagens

1997 ◽  
Vol 273 (4) ◽  
pp. L726-L732 ◽  
Author(s):  
Naveed Hussain ◽  
Fengying Wu ◽  
Constance Christian ◽  
Mitchell J. Kresch
Keyword(s):  
Steady State ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Type I ◽  
Fibroblast Proliferation ◽  
Rat Lung ◽  
Collagen Production ◽  
Fetal Rat ◽  
Fetal Rat Lung ◽  
Steady State Levels

The direct effects of hyperoxia on collagen production by fetal lung fibroblasts are unknown and would be important to the understanding of the molecular mechanisms involved in bronchopulmonary dysplasia in premature infants. We studied the effect of hyperoxia on 1) proliferation, 2) mRNA levels for type I and III procollagens, and 3) net collagen production in primary cultures of fetal rat lung fibroblasts. Fibroblasts from 19-day-old rat fetuses (term is 22 days) were obtained. Test plates were incubated in hyperoxia and controls in room air for varying time periods. Cell viability in both conditions was >97% as determined by trypan blue exclusion. Fibroblast proliferation in nonconfluent cultures was found to be significantly reduced with exposure to hyperoxia ( P< 0.001). Steady-state levels of type I and III procollagen mRNAs, analyzed on Northern blots hybridized to [32P]cDNA probes, were significantly decreased in hyperoxia ( P < 0.01). This effect was noted as early as 4 h of exposure to hyperoxia and persisted for 5 days. There was a significant inverse correlation between duration of exposure to O2 and steady-state levels of mRNA for α1(I)-procollagen ( r = −0.904) and α1(III)-procollagen ( r = −0.971). There were no significant changes in steady-state levels of β-actin mRNA. We also found a significant decrease in collagen synthesis in hyperoxia-exposed fibroblasts ( P < 0.05). We conclude that hyperoxia directly effects a reduction in fetal lung fibroblast proliferation and net collagen production at a pretranslational level.

Sex hormones regulate CFTR in developing fetal rat lung epithelial cells

1997 ◽  
Vol 272 (5) ◽  
pp. L844-L851 ◽  
Author(s):  
N. B. Sweezey ◽  
F. Ghibu ◽  
S. Gagnon
Keyword(s):  
Epithelial Cells ◽  
Sex Hormones ◽  
Functional Activity ◽  
Lung Development ◽  
Fetal Lung ◽  
Lung Epithelial Cells ◽  
Rat Lung ◽  
Fetal Rat ◽  
Lung Epithelial ◽  
Fetal Rat Lung

Sex hormones modulate two normal processes of late-gestation mammalian lung development: the onset of augmented production of surfactant phospholipids and the loss of mesenchymal cells. As prenatal lung development advances, epithelial chloride secretory pathways diminish as opposing sodium absorptive pathways increase in expression. We hypothesized that sex hormones may influence both the gene expression and functional activity of the chloride channel known as the cystic fibrosis transmembrane conductance regulator (CFTR) in fetal lung epithelium. We report here that sex hormones exert opposite effects on CFTR. Androgen increases and estrogen decreases CFTR functional activity [as assessed by CFTR antisense (but not sense) oligodeoxynucleotide-sensitive adenosine 3',5'-cyclic monophosphate-stimulated cell volume reduction or by glibenclamide-sensitive, amiloride-insensitive transepithelial electrical potential] in primary cultures of fetal rat lung epithelial cells. No alterations in CFTR mRNA levels measured by quantitative polymerase chain reaction amplification of reverse transcripts) accompanied either the changes in functional activity induced by sex hormones or the changes observed during normal development, suggesting that sex hormone modulation of CFTR in antenatal lung occurs at a posttranscriptional level. Our data are consistent with the hypothesis that both androgen and estrogen contribute to the male disadvantage with respect to fetal lung functional development.

Growth of distal fetal rat lung epithelial cells in a defined serum-free medium

1991 ◽  
Vol 27 (8) ◽  
pp. 625-632 ◽  
Author(s):  
D. Jassal ◽  
R. N. N. Han ◽  
I. Caniggia ◽  
M. Post ◽  
A. K. Tanswell
Keyword(s):  
Epithelial Cells ◽  
Lung Epithelial Cells ◽  
Rat Lung ◽  
Serum Free Medium ◽  
Free Medium ◽  
Serum Free ◽  
Fetal Rat ◽  
Lung Epithelial ◽  
Fetal Rat Lung

168 THY-1 EXPRESSION IS ASSOCIATED WITH UP-REGULATION OF WNT SIGNALING AND MYOFIBROBLAST PHENOTYPE IN FETAL RAT LUNG FIBROBLASTS.

2006 ◽  
Vol 54 (1) ◽  
pp. S109.2-S109
Author(s):  
C. Dasgupta ◽  
Y. Wang ◽  
R. Sakurai ◽  
J. Santos ◽  
J. S. Torday ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Lung Fibroblasts ◽  
Rat Lung ◽  
Myofibroblast Phenotype ◽  
Fetal Rat ◽  
Fetal Rat Lung

scholarly journals Leptin mediates the parathyroid hormone-related protein paracrine stimulation of fetal lung maturation

2002 ◽  
Vol 282 (3) ◽  
pp. L405-L410 ◽  
Author(s):  
J. S. Torday ◽  
H. Sun ◽  
L. Wang ◽  
E. Torres
Keyword(s):  
De Novo ◽  
Fetal Lung ◽  
Lung Fibroblasts ◽  
Type Ii ◽  
Rat Lung ◽  
Parathyroid Hormone Related Protein ◽  
Fetal Rat ◽  
Type Ii Cell ◽  
Leptin Expression ◽  
Stimulation Of

Developing rat lung lipofibroblasts express leptin beginning on embryonic day (E) 17, increasing 7- to 10-fold by E20. Leptin and its receptor are expressed mutually exclusively by fetal lung fibroblasts and type II cells, suggesting a paracrine signaling “loop.” This hypothesized mechanism is supported by the following experimental data: 1) leptin stimulates the de novo synthesis of surfactant phospholipid by both fetal rat type II cells (400% · 100 ng−1 · ml−1 · 24 h−1) and adult human airway epithelial cells (85% · 100 ng−1 · 24 h−1); 2) leptin is secreted by lipofibroblasts in amounts that stimulate type II cell surfactant phospholipid synthesis in vitro; 3) epithelial cell secretions such as parathyroid hormone-related protein (PTHrP), PGE2, and dexamethasone stimulate leptin expression by fetal rat lung fibroblasts; 4) PTHrP or leptin stimulate the de novo synthesis of surfactant phospholipid (2- to 2.5-fold/24 h) and the expression of surfactant protein B (SP-B; >25-fold/24 h) by fetal rat lung explants, an effect that is blocked by a leptin antibody; and 5) a PTHrP receptor antagonist inhibits the expression of leptin mRNA by explants but does not inhibit leptin stimulation of surfactant phospholipid or SP-B expression, indicating that PTHrP paracrine stimulation of type II cell maturation requires leptin expression by lipofibroblasts. This is the first demonstration of a paracrine loop that functionally cooperates to induce alveolar acinar lung development.

scholarly journals Fetal rat lung epithelium has a functional growth hormone receptor coupled to tyrosine kinase activity and insulin-like growth factor binding protein-2 production

1998 ◽  
Vol 21 (1) ◽  
pp. 73-84 ◽  
Author(s):  
DC Batchelor ◽  
RM Lewis ◽  
BH Breier ◽  
PD Gluckman ◽  
SJ Skinner
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Binding Protein ◽  
Fetal Lung ◽  
Mrna Levels ◽  
Insulin Like Growth Factor ◽  
Rat Lung ◽  
Lung Epithelium ◽  
Fetal Rat ◽  
Fetal Rat Lung

Although growth hormone (GH) receptor (GHR) mRNA and protein are present in fetal tissues such as the lung, there is little evidence that GH mediates growth in the fetus. We have identified functional responses to GH in fetal rat lung epithelia and suggest a possible role for GHR in the developing lung. GHR mRNA in lung extracts was high before birth at day 16 of gestation (16f), decreased to low levels at day 22f but increased again after birth. At day 20f GHR mRNA levels were higher in lung than in liver, whereas growth hormone binding protein mRNA levels were approximately equal in lung and liver. Stimulation of primary cell cultures of day 19f lung epithelia with GH caused increased tyrosine phosphorylation in specific proteins, demonstrating functional GHR. Lung fibroblasts isolated at the same time did not respond to GH. Ligand and Northern blot analysis of the epithelial cultures revealed that GH stimulation increased insulin-like growth factor binding protein-2 (IGFBP-2) activity and mRNA. These experiments demonstrate the functional activity of GHR, specifically in fetal lung epithelium. We suggest that one role for GH in vivo may be indirectly to modify insulin-like growth factor activity in the developing fetal lung by increasing IGFBP-2.

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